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METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure (METIS Trial)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daniel Medeiros Moreira, Instituto de Cardiologia do Rio Grande do Sul
ClinicalTrials.gov Identifier:
NCT00759811
First received: September 24, 2008
Last updated: March 29, 2013
Last verified: March 2013
  Purpose

The aim of the study is to evaluate the efficacy of methotrexate to improve physical capacity in patients with symptomatic ischemic heart failure.


Condition Intervention Phase
Heart Failure
Myocardial Ischemia
Drug: Methotrexate
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)

Resource links provided by NLM:


Further study details as provided by Instituto de Cardiologia do Rio Grande do Sul:

Primary Outcome Measures:
  • Change in Physical Capacity Measured Using the 6-minute Walk Test Distance [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    The primary outcome of the study was the difference in 6MWT distance before and after the treatment (change in meters evaluated by t test).


Secondary Outcome Measures:
  • Improve in Heart Failure Functional Class Measured Using New York Heart Association [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Improve in Quality of Life Measured Using the Brazilian Edition SF-36 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Incidence of Adverse Effects of the Treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: December 2007
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methotrexate
Patients receiving conventional treatment to heart failure who will receive methotrexate 7.5mg oral plus folic acid 5mg oral once a week for 12 weeks.
Drug: Methotrexate

Patients receiving conventional treatment to heart failure who will receive methotrexate 7.5mg oral plus folic acid 5mg oral once a week for 12 weeks.

All patients will have evaluated at the baseline and after 12 weeks: physical capacity by the 6-minutes walk test, quality of life by the Brazilian edition SF-36 and inflammatory marker by C-reactive protein. They also will be tested for ALT, AST, blood cell count, creatinine, and prothrombin time at baseline, after 6 weeks and after 12 weeks.

Other Names:
  • Rheumatrex
  • Trexall
Placebo Comparator: Placebo
Patients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks.
Drug: Placebo

Patients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks.

All patients will have evaluated at the baseline and after 12 weeks: physical capacity by the 6-minutes walk test, quality of life by the Brazilian edition SF-36 and inflammatory marker by C-reactive protein. They also will be tested for ALT, AST, blood cell count, creatinine, and prothrombin time at baseline, after 6 weeks and after 12 weeks.

Other Names:
  • Placebo
  • Control

Detailed Description:

Recent studies have showed the importance of proinflammatory mediators in the heart failure. However, there is a lack of benefit of therapies that tried to neutralize these mediators.

Methotrexate has adenosine-mediated anti-inflammatory effects in rheumatoid arthritis and psoriasis. Methotrexate limits infarct size via this adenosine-dependent mechanisms in heart of dogs (J Cardiovasc Pharmacol. 2004 Apr;43(4):574-9). A recent trial showed that this drug reduced proinflammatory mediators in patients with heart failure (Am Heart J. 2006 Jan;151(1):62-8).

These data suggest that methotrexate may improve physical capacity in patients ischemic heart failure reducing inflammation, but a randomized clinical trial is necessary to prove it.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Heart failure functional class measured using the New York Heart Association classification class II, III or IV
  • Left ventricular fraction <0.45 at the ventriculography
  • Angiographic coronary lesions higher than 50% or coronary lesion revascularized (coronary artery bypass or percutaneous transluminal coronary angioplasty)

Exclusion Criteria:

  • Myocardial infarction in the past four months
  • Coronary artery bypass or percutaneous transluminal coronary angioplasty in the past four months
  • Left ventricular disfunction diagnosed during a acute coronary syndrome
  • Those who require revascularization in the following 12 weeks
  • Hepatic disease (ALT and AST higher than the upper limit of the reference value)
  • Renal failure (plasma creatinine higher than 2.0mg/dl)
  • Alcoholism (20 doses per week or more)
  • Illegal drug use
  • Rheumatoid arthritis or other inflammatory diseases
  • Infectious disease
  • Neoplasm
  • Anemia (hematocrit lower than 30%)
  • Currently on any anti-inflammatory drugs
  • Difficulty in walking
  • Unable to understand/complete the 36-item Short Form health survey (SF-36)
  • Those who do not give informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00759811

Locations
Brazil
Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
Porto Alegre, Rio Grande do Sul, Brazil, 90620001
Sponsors and Collaborators
Instituto de Cardiologia do Rio Grande do Sul
Investigators
Study Director: Carlos AM Gottschall, MD MSc PhD Instituto de Cardiologia do Rio Grande do Sul
Principal Investigator: Daniel M Moreira, MD Instituto de Cardiologia do Rio Grande do Sul
Study Director: Jefferson L Vieira, MD Instituto de Cardiologia do Rio Grande do Sul
  More Information

Publications:
Moreira DM, Vieira JL, Gottschall CAM. The Effects of METhotrexate Therapy on the Physical Capacity of Patients With ISchemic Heart Failure: A Randomized Double-Blind, Placebo-Controlled Trial (METIS Trial). Journal of Cardiac Failure. Article in Press

Responsible Party: Daniel Medeiros Moreira, MSc., Instituto de Cardiologia do Rio Grande do Sul
ClinicalTrials.gov Identifier: NCT00759811     History of Changes
Other Study ID Numbers: UP4062
Study First Received: September 24, 2008
Results First Received: September 4, 2009
Last Updated: March 29, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by Instituto de Cardiologia do Rio Grande do Sul:
Heart Failure
Myocardial Ischemia
Methotrexate
Inflammation
Anti-Inflammatory Agents
Inflammation Mediators

Additional relevant MeSH terms:
Coronary Artery Disease
Heart Failure
Ischemia
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Pathologic Processes
Vascular Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014